Article
Chemistry, Multidisciplinary
Shih-Hsun Cheng, M. Reid Groseclose, Cindy Mininger, Mats Bergstrom, Lily Zhang, Stephen C. Lenhard, Tinamarie Skedzielewski, Zachary D. Kelley, Debra Comroe, Hyundae Hong, Haifeng Cui, Jennifer L. Hoover, Steve Rittenhouse, Stephen Castellino, Beat M. Jucker, Hasan Alsaid
Summary: This study developed a multimodal imaging approach to assess the distribution of an antibacterial drug delivered as a liposomal formulation in a mouse infection model. By combining positron emission tomography (PET) and matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS), the researchers observed an excellent correlation between the radiolabel signal detected by PET and the drug and lipid component signals detected by MALDI IMS.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Biochemistry & Molecular Biology
Andreas Dannhorn, Maria Luisa Doria, James McKenzie, Paolo Inglese, John G. G. Swales, Gregory Hamm, Nicole Strittmatter, Gareth Maglennon, Sadaf Ghaem-Maghami, Richard J. A. Goodwin, Zoltan Takats
Summary: In this study, a method called analyte-targeted DESI-MSI utilizing a TQ mass analyzer was used for faster MSI data acquisition. The platform operated successfully at a scanning rate of 10 scans/s, offering improved sensitivity compared to conventional TOF mass analyzers. It has the potential for pharmaceutical research and development, as it enhances compound coverage and reduces dataset size.
Review
Chemistry, Analytical
Jonatan Riber Granborg, Anne Mette Handler, Christian Janfelt
Summary: New mass spectrometry imaging (MSI) techniques are gaining importance in various stages of drug discovery and development, as well as in fundamental studies of drug delivery. MSI provides high selectivity and enables simultaneous imaging of drugs, metabolites, and endogenous biomarkers. This review focuses on the application of MSI in drug imaging, particularly in drug distribution and metabolism studies. It covers the principles of MSI, sample preparation, data analysis, and quantitative MSI. The review also presents examples of pharmaceutical applications of MSI, highlighting its contribution to obtaining information not readily obtainable by conventional analytical techniques. The paper concludes with an overview of ongoing trends in MSI and future directions.
TRAC-TRENDS IN ANALYTICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Niels Bjerre Holm, Maria Deryabina, Carsten Boye Knudsen, Christian Janfelt
Summary: Therapeutic peptides are an important class of pharmaceuticals with significant costs associated with their discovery and development. This study used mass spectrometry imaging (MSI) to investigate the absorption, distribution, metabolism, and excretion (ADME) characteristics of a peptide drug, cyclosporine (CsA). The results showed widespread distribution of CsA in mouse organs, with its metabolites predominantly detected in the intestines. MSI could provide valuable insights for ADME studies, especially in the early stages of drug development.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Andreas Dannhorn, Emine Kazanc, Gregory Hamm, John G. Swales, Nicole Strittmatter, Gareth Maglennon, Richard J. A. Goodwin, Zoltan Takats
Summary: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a commonly used tool in pharmacokinetic (PK) studies for the quantification of drugs. However, it lacks spatial information. In this study, mass spectrometry imaging (MSI) was used to determine the distributions and abundances of benchmarking compounds in rat intestine, providing insights into the spatial distribution of drugs in different histological compartments. The correlation between MSI data and absolute tissue concentrations of the benchmark compounds validates the quantitative relation of the imaging data, allowing for relative quantification of compounds within and between tissues.
Article
Engineering, Biomedical
Francesca Razzi, Matija Lovrak, Dovile Gruzdyte, Yvette Den Hartog, Dirk J. Duncker, Jan H. van Esch, Volkert van Steijn, Heleen M. M. van Beusekom
Summary: This study aimed to create an artificial atherosclerotic plaque with reproducible and controllable complexity for systematic studies on drug transport in stented arteries. The results showed that the lipid-rich artificial plaque significantly hampers drug transport, highlighting the importance of studying drug transport phenomena in the presence of lipids.
ADVANCED HEALTHCARE MATERIALS
(2022)
Review
Chemistry, Multidisciplinary
Muhammad Ramzan, Ali Raza, Zaib Un Nisa, Syed Ghulam Musharraf
Summary: The continuous development of resistance to antibiotic drugs by microorganisms causes high mortality and morbidity. Pathogens with distinct features and biochemical abilities make them destructive to human health. Therefore, early identification of the pathogen is of substantial importance for quick ailments and healthcare outcomes. Several advanced spectroscopic techniques have been utilized for the identification of microorganisms, particularly bacteria, in research studies conducted in the last five years. Among these techniques, mass spectrometry (MS), infrared (IR) spectroscopy, Raman spectroscopy (RS), and nuclear magnetic resonance (NMR) spectroscopy have been widely used. MALDI-TOF/MS, a type of MS technique, has been particularly favored for microbial identification. The review discusses the identification of 44 bacteria using these techniques, with the most studied organisms being E. coli, S. aureus, and other microorganisms.
ARABIAN JOURNAL OF CHEMISTRY
(2023)
Article
Environmental Sciences
Yu Bian, Mu-Yi He, Yun Ling, Xiu-Juan Wang, Feng Zhang, Xue-Song Feng, Yuan Zhang, Shi-Ge Xing, Jie Li, Xin Qiu, Yu-Rui Li
Summary: The study introduced a new strategy to investigate the distribution of PFOA in tissues and estimate the exposure stages, using MALDI-MSI method to monitor the spatio-temporal distribution of PFOA in zebrafish tissues. By analyzing the law of change obtained from high spatial resolution MSI data, two different enrichment trends in ten tissues were summarized by curve fitting, defining a new exposure curve to evaluate the exposure stages. With this model, three levels (mild, moderate, and deep pollution stage) of PFOA pollution in zebrafish can be simply evaluated.
ENVIRONMENTAL POLLUTION
(2022)
Article
Chemistry, Analytical
Bo-Jhang Lin, Tien-Chueh Kuo, Hsin-Hsiang Chung, Ying-Chen Huang, Ming-Yang Wang, Cheng-Chih Hsu, Po-Yang Yao, Yufeng Jane Tseng
Summary: Mass spectrometry imaging (MSI) is a powerful tool for investigating the spatial distribution of molecules in samples. However, analyzing complex biological systems often requires multiple analytical techniques. Image registration is a critical step for combining MSI with other imaging techniques, but it can be challenging due to differences in spatial resolution and image characteristics. In this study, a web service called MSI Registrar (MSIr) was developed for automatic registration between MSI and histology, providing a more objective and efficient way to analyze molecular components in tissues.
ANALYTICAL CHEMISTRY
(2023)
Article
Agriculture, Multidisciplinary
Yan-Xia Zhang, Yi-Da Zhang, Yan-Ping Shi
Summary: Exploring the spatial distribution alterations of metabolites during lentil germination is crucial for understanding its nutritional value, physiological function, and metabolic pathway. This study established an effective MALDI-MSI method to visualize the changes in spatial localization of 53 metabolites in lentils during germination. The results showed specific distribution patterns of different metabolites, with certain lipids mainly located in the cotyledons and others spreading throughout the lentil tissue during early germination. Heat map analysis demonstrated the correlation between lipid content changes and germination time, supporting the potential use of germinated lentils as nutraceutical or functional food.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Biophysics
Heesang Ahn, Soojung Kim, Yoonhee Kim, Seungchul Kim, Jong-Ryul Choi, Kyujung Kim
Summary: The study explores three plasmonic modalities as tools to study neurons and their responses, demonstrating the potential of plasmonic sensing, imaging, and stimulation techniques to effectively study neurons and understand their specific molecular activities.
BIOSENSORS & BIOELECTRONICS
(2021)
Article
Pharmacology & Pharmacy
Anusha Balla, Seppo Auriola, Angus C. Grey, Nicholas J. Demarais, Annika Valtari, Emma M. Heikkinen, Elisa Toropainen, Arto Urtti, Kati-Sisko Vellonen, Marika Ruponen
Summary: The study investigated the partitioning of seven beta-blocking drugs in different ocular tissues and found a positive correlation between drug distribution and lipophilicity. The application of MALDI-IMS technology allowed for simultaneous detection of drug compounds in the cornea and revealed uneven drug distribution. The results highlight the importance of lipophilicity in defining corneal pharmacokinetics and suggest that K-p values are useful for kinetic simulation models in topical ocular drug administration.
Article
Food Science & Technology
Daria Kucheriavaia, Dusan Velickovic, Nicholas Peraino, Apurva Lad, David J. Kennedy, Steven T. Haller, Judy A. Westrick, Dragan Isailovic
Summary: This study investigated the distribution of MC-LR in liver tissues of mice using MALDI-FT-ICR-MS imaging techniques. The results show that high-resolution MALDI-MS imaging can monitor the distribution of free microcystins in affected organs.
Article
Chemistry, Analytical
Lennart R. S. Huizing, James McDuffie, Filip Cuyckens, Marjolein van Heerden, Tatiana Koudriakova, Ron M. A. Heeren, Rob J. Vreeken
Summary: This study investigated the distribution of tofacitinib in the intestines of rats using mass spectrometry imaging, finding the highest signal in the ileum at 1 hour and in the colon at 7 hours post-dose. Through 3D intensity plots and tissue stains, a gradual decrease in tofacitinib concentration from the lumen towards the muscular layer of the proximal colon was visually observed.
ANALYTICAL CHEMISTRY
(2021)
Article
Food Science & Technology
Mudita Vats, Berta Cillero-Pastor, Bryn Flinders, Eva Cuypers, Ron M. A. Heeren
Summary: This study utilized MALDI-MSI to determine the spatial distribution of flavor compounds in edible button mushrooms and optimized the sample preparation protocol and investigated the effect of heat on the distribution.
JOURNAL OF FOOD SCIENCE AND TECHNOLOGY-MYSORE
(2023)
Article
Chemistry, Medicinal
Nicolas Kraupner, Chau Phi Dinh, Xiaoan Wen, Valerie Landry, Adrien Herledan, Florence Leroux, Damien Bosc, Julie Charton, Clara Maillard, Sandrine Warenghem, Isabelle Duplan, Catherine Piveteau, Nathalie Hennuyer, Bart Staels, Benoit Deprez, Rebecca Deprez-Poulain
Summary: Insulin degrading enzyme (IDE) is linked to the risk of type-2 diabetes (T2D) or Alzheimer's disease (AD). Activating IDE could be a potential therapeutic strategy for AD and also beneficial in diabetes.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Neurosciences
Benjamin Deckmyn, Dorothee Domenger, Chloe Blondel, Sarah Ducastel, Emilie Nicolas, Emilie Dorchies, Emilie Caron, Julie Charton, Emmanuelle Vallez, Benoit Deprez, Jean-Sebastien Annicotte, Sophie Lestavel, Anne Tailleux, Christophe Magnan, Bart Staels, Kadiombo Bantubungi
Summary: A study found that activation of the nuclear bile acid receptor in the brain can modify energy homeostasis by affecting the function of brown adipose tissue. Activation of brain FXR decreases the rate-limiting enzyme in catecholamine synthesis, which in turn reduces sympathetic tone. This research sheds new light on the complex control of energy homeostasis by bile acids through FXR.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Cell Biology
Marion Flipo, Rosangela Frita, Marilyne Bourotte, Maria S. Martinez-Martinez, Markus Boesche, Gary W. Boyle, Geo Derimanov, Gerard Drewes, Pablo Gamallo, Sonja Ghidelli-Disse, Stephanie Gresham, Elena Jimenez, Jaime de Mercado, Esther Perez-Herran, Esther Porras-De Francisco, Joaquin Rullas, Patricia Casado, Florence Leroux, Catherine Piveteau, Mehdi Kiass, Vanessa Mathys, Karine Soetaert, Veronique Megalizzi, Abdalkarim Tanina, Rene Wintjens, Rudy Antoine, Priscille Brodin, Vincent Delorme, Martin Moune, Kamel Djaout, Stephanie Slupek, Christian Kemmer, Marc Gitzinger, Lluis Ballell, Alfonso Mendoza-Losana, Sergio Lociuro, Benoit Deprez, David Barros-Aguirre, Modesto J. Remuinan, Nicolas Willand, Alain R. Baulard
Summary: The compound SMARt751, which interacts with the transcriptional regulator of M. tuberculosis, was found to enhance the efficacy of ethionamide and restore its effectiveness in ethionamide-resistant strains. The compound was also shown to be safe in both in vitro and in vivo tests. A model predicted that a daily dose of 25 mg of SMARt751 would enable a significant reduction in the dose of ethionamide administered while maintaining the same efficacy and reducing side effects.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Chemistry, Medicinal
Kevin Antraygues, Nina Compagne, Francesca Ruggieri, Kamel Djaout, Zainab Edoo, Maxime Eveque, Leo Faion, Bruna Gioia, Salia Tangara, Anais Vieira Da Cruz, Baptiste Villemagne, Marion Flipo, Alain Baulard, Nicolas Willand
Summary: This article summarizes the joint autumn symposium organized by the French Society for Medicinal Chemistry and the French Microbiology Society, which attracted over 200 researchers from France and abroad, generating high-level scientific dialogue on the most recent advances in combating antimicrobial resistance.
Article
Chemistry, Medicinal
Kevin Antraygues, Mathieu Maingot, Birgit Schellhorn, Vincent Trebosc, Marc Gitzinger, Benoit Deprez, Olivier Defert, Glenn E. Dale, Marilyne Bourotte, Sergio Lociuro, Nicolas Willand
Summary: In this study, the objective was to design and synthesize rifabutin prodrugs with increased aqueous solubility for intravenous use. Seventeen prodrugs were synthesized using developed synthetic methodologies, and their water solubility, stability in plasma, and antimicrobial activity against A. baumannii were evaluated. A pharmacokinetic release study in CD1 mice demonstrated the successful release of active rifabutin from selected prodrugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Analytical
Annick Menetrey, Raphael Legouffe, Amina Haouala, David Bonnel, Elisabeth Rouits, Jacques Bosq, Jonathan Stauber
Summary: As tumors are heterogeneous, investigating drug penetration and concentration in different regions of the tumor is crucial. Quantitative mass spectrometry imaging (QMSI) allows for accurate evaluation of drug efficacy and safety.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Sushovan Dam, Salia Tangara, Claire Hamela, Theo Hattabi, Leo Faion, Paul Carre, Rudy Antoine, Adrien Herledan, Florence Leroux, Catherine Piveteau, Maxime Eveque, Marion Flipo, Benoit Deprez, Laurent Kremer, Nicolas Willand, Baptiste Villemagne, Ruben C. Hartkoorn
Summary: A promising class of compounds called TriSLas has been discovered, showing activity against Mycobacterium tuberculosis by acting as inhibitors of the Ndh-2 enzyme. These compounds increase the NADH/NAD+ ratio and decrease ATP levels in bacteria, providing a new strategy for combating multidrug-resistant strains.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
M. Maingot, M. Bourotte, A. C. Vetter, C. B. Schellhorn, K. Antraygues, H. Scherer, M. Gitzinger, C. Kemmer, G. E. Dale, O. Defert, S. Lociuro, M. Bronstrup, N. Willand, V. Trebosc
Summary: Hospital-acquired infections are increasing and becoming a burden on both clinical practice and finances. Acinetobacter baumannii infections are particularly difficult to treat due to their high level of resistance to antibiotics. A recent study found that the antibiotic rifabutin showed potent activity against extensively drug resistant A. baumannii. Further research focused on synthesizing rifabutin analogs and found that their efficacy in A. baumannii was not reflected in other bacteria. The study also identified the structural features necessary for strong accumulation of rifabutin in A. baumannii.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Lucile Brier, Haitham Hassan, Xavier Hanoulle, Valerie Landry, Danai Moschidi, Lowiese Desmarets, Yves Rouille, Julie Dumont, Adrien Herledan, Sandrine Warenghem, Catherine Piveteau, Paul Carr, Sarah Ikherbane, Francois-Xavier Cantrelle, Elian Dupre, Jean Dubuisson, Sandrine Belouzard, Florence Leroux, Benoit Deprez, Julie Charton
Summary: Since the end of 2019, the global outbreak of the coronavirus SARS-CoV-2 has caused a significant increase in infections and deaths worldwide. Researchers have identified two proteases, 3CLpro and papain-like protease, encoded by the virus that play a crucial role in the virus lifecycle. Targeting the 3CLpro, which is highly conserved within this viral family, a screening of over 89,000 small molecules led to the discovery of a potent inhibitor of the SARS-CoV-2 3CLpro. The mechanism of inhibition, interaction with the protease, specificity against host proteases, and promising antiviral properties in cells are reported.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Clement Philippe Delannoy, Egon Heuson, Adrien Herledan, Frederik Oger, Bryan Thiroux, Mickael Chevalier, Xavier Gromada, Laure Rolland, Philippe Froguel, Benoit Deprez, Sebastien Paul, Jean-Sebastien Annicotte
Summary: Type 2 diabetes is a metabolic disorder affecting over 537 million people worldwide, characterized by loss of pancreatic beta-cell function and insulin resistance. Long-term control of glycemia is challenging, highlighting the need for new drugs and targets to improve beta-cell function and insulin secretion. In this study, a high-throughput screening method using automated cellular assays and mass spectrometry was developed, identifying potential regulators of insulin secretion and synthesis among siRNA and chemical compounds.
Article
Chemistry, Medicinal
Francesca Ruggieri, Philippe Hance, Bruna Gioia, Alexandre Biela, Pascal Roussel, Jean-Louis Hilbert, Nicolas Willand
Summary: This study describes a novel three-step large-scale extraction and purification method for the simultaneous purification of 11,13-dihydrolactucin (DHLc) and lactucin (Lc) from a chicory genotype rich in these sesquiterpene lactones (STLs) and their glucosyl and oxalyl conjugated forms. The results will facilitate the evaluation of the biological potential of chicory-derived STLs and their semisynthetic analogues.
Article
Chemistry, Medicinal
Salia Tangara, Leo Faion, Catherine Piveteau, Frederic Capet, Romain Godelier, Marion Michel, Marion Flipo, Benoit Deprez, Nicolas Willand, Baptiste Villemagne
Summary: The concept of privileged structure is an effective method for discovering new biologically active molecules. It refers to a semi-rigid scaffold capable of displaying substituents in multiple spatial directions to provide potent and selective ligands for different biological targets. These structures tend to have improved drug-like properties and are therefore attractive starting points for optimization programs. This article presents a rapid, reliable, and efficient synthesis of novel three-dimensional bio-inspired tricyclic spirolactams and analyzes their drug-like properties.
Article
Chemistry, Medicinal
Leo Faion, Kamel Djaout, Catalin Pintiala, Catherine Piveteau, Florence Leroux, Alexandre Biela, Stephanie Slupek, Rudy Antoine, Monika Zahorszka, Francois-Xavier Cantrelle, Xavier Hanoulle, Jana Kordulakova, Benoit Deprez, Nicolas Willand, Alain R. Baulard, Marion Flipo
Summary: Mycobacterium tuberculosis causes 1.5 million deaths annually and drug-resistant strains are increasing. Discovery of molecules targeting new M. tuberculosis targets is crucial. Anthranilic acids have been identified as MabA inhibitors, and their structure-activity relationships, binding to MabA, physico-chemical properties, and antimycobacterial activity have been investigated. These compounds affect multiple targets in mycobacterial cells and their antituberculous activity is attributed to their carboxylic acid moiety.
Article
Multidisciplinary Sciences
Olivier Songue Same, Catherine Piveteau, Alexandre Biela, Richard Kamga, Benoit Deprez
Summary: This study aims to assess the levels of bisphenols in sachet water, bagged whisky, crude palm oil, and traditional alcoholic beverages in Cameroon. The research found that the detection limits of bisphenol A, B, and F in water samples were 0.09, 0.10, and 0.09 μg/L, respectively. It was also discovered that one brand of sachet water contained 14.5 μg/L of bisphenol F.
SCIENTIFIC AFRICAN
(2023)
Review
Chemistry, Medicinal
Francesca Ruggieri, Nina Compagne, Kevin Antraygues, Maxime Eveque, Marion Flipo, Nicolas Willand
Summary: Antimicrobial resistance (AMR) is a major public health issue causing 5 million deaths per year. To combat this problem, new antibiotics with novel targets or modes of action are needed. Promising compounds such as gepotidacin, zoliflodacin, ibezapolstat, MGB-BP-3, CRS-3123, afabicin, TXA-709, and recently approved lefamulin have shown potential in clinical trials. This review provides information on the chemical synthesis, mode of action, structure-activity relationships, in vitro and in vivo activities, and clinical data of these eight small molecules.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
